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Biomedical subjects

S Majumdar

Publications and source records attributed to S Majumdar.

At least 109 records · Page 6Linked to original sources

Evidence for a Menkes-like protein with a nuclear targeting sequence.

Extracts from three human cell lines were found to contain abridged Menkes disease gene transcripts with novel insertion sequences. The transcript variant that is the focus of the present study codes for a 103-residue protein containing the first heavy-metal-binding domain (Hmb1) of ATP7A, the Cu-ATPase associated with Menkes disease. This transcript variant has a 45-bp nucleotide insert interposed between exons 1 and 2 of ATP7A that starts with a 5' ATG that is in-frame with the downstream ATG translation start site of ATP7A. We report here that the 66-bp nucleotides positioned between the upstream and downstream ATG sites encode 22 amino acid residues whose primary structure in part meets the criteria for a nuclear-localization sequence (NLS). We have referred to the transcript as nuclear Menkes-like (NML) 45. A green fluorescent protein (GFP) construct with NML45 when transfected in Chinese hamster ovary cells localized to the cell nucleus. A similar construct without the 66-bp segment exhibited a random dispersed fluorescent pattern in the cytosol. GFP constructs encoding ATP7A exons likewise failed to direct GFP into the cell nucleus, suggesting the nuclear determinant is not in an internal domain of the protein. The data suggest that the 22-residue segment contains an NLS for an 11.2-kDa protein with one Cu-binding site that may function as a chaperone to transport Cu into the nucleus of mammalian cells.

Adenosine Triphosphatases↗

Magnetization transfer ratio in new MS lesions before and during therapy with IFNbeta-1a.

OBJECTIVE: The authors examined the effect of 6.0 MIU interferon beta-1a (IFNbeta-1a) administered IM each week on the evolution of monthly magnetization transfer ratio (MTR) within new gadolinium-enhancing (Gd+) lesions in patients with very early relapsing-remitting (RR) MS. BACKGROUND: IFNbeta is an effective disease-modifying treatment for patients with RRMS. Among other effects, it has been shown to decrease the number of new Gd+ and T2-weighted lesions. MTR is a putative marker for irreversible tissue damage and evolution of MTR within a lesion may reflect recovery of tissue damage. It is not known whether IFNbeta-1a affects the recovery phase of lesions. METHODS: Eight untreated patients with RRMS who completed up to 14 monthly brain MRI sessions elected to initiate treatment with IFNbeta-1a. Four out of eight patients developed new Gd+ lesions during treatment. MTR of lesions at the time of appearance and subsequent rate of change of monthly MTR were compared before and after treatment (stratified Mann-Whitney test). RESULTS: The difference between MTR at appearance of 47 new Gd+ lesions before treatment versus 23 new Gd+ lesions during treatment was not significant. Twenty-two of 47 new Gd+ lesions before treatment and 11 of 23 new Gd+ lesions after treatment were monitored for up to 6 months. After appearance of new Gd+ lesions, the rate of increase in MTR was faster during therapy (p = 0.037). CONCLUSION: MTR abnormalities within new Gd+ lesions evolve at a faster rate during treatment with IFNbeta-1a than before initiating therapy. This is consistent with the hypothesis that IFNbeta-1a promotes resolution of new Gd+ lesions.

Adjuvants, Immunologic↗

Studies on the relationships between the synonymous codon usage and protein secondary structural units.

The relationship between the synonymous codon usage and protein secondary structural elements (alpha helices and beta sheets) were reinvestigated by taking structural information of proteins from Protein Data Bank (PDB) and their corresponding mRNA sequences from GenBank for four different organisms E. coli, B. subtilis, S. cerevisiae, and Homo sapiens. It was observed that synonymous codon families have non-random codon usage, but there does not exist any species invariant universal correlation between the synonymous codon usage and protein secondary structural elements. The secondary structural units of proteins can be distinguished from the occurrences of bases at the second codon position.

Amino Acids↗

Interferon-gamma- and lipopolysaccharide-induced tumor necrosis factor-alpha is required for nitric oxide production: tumor necrosis factor-alpha and nitric oxide are independently involved in the killing of Mycobacterium microti in interferon-gamma- and lipopolysaccharide-treated J774A.1 cells.

A comparative study was done using J774A.1 and J774A.1-derived transfected cells (J774A.1 C.1) containing antisense tumor necrosis factor alpha (TNF-alpha) plasmid to determine the role of endogenous TNF-alpha on nitric oxide production as well as on the growth of Mycobacterium microti in interferon gamma (IFN-gamma)- and lipopolysaccharide (LPS)-treated cells. On stimulation with IFN-gamma and LPS a higher level of NO was observed in J774A.1 cells compared to J774A.1 C.1 which indicated that endogenous TNF-alpha is required for the production of NO. Comparing the effect of IFN-gamma and LPS on the intracellular growth of M. microti, the growth-reducing activity was higher in J774A.1 cells than in J774A.1 C.1 cells and was not completely abrogated in the presence of the nitric oxide inhibitor NG-methyl-L-arginine (L-NMA). J774A.1 C.1 cells infected with M. microti produced a significant amount of NO when exogenous TNF-alpha was added along with IFN-gamma and LPS and the concentration of intracellular bacteria decreased almost to that in IFN-gamma and LPS treated parental J774A.1 cells. Addition of exogenous TNF-alpha even in the presence of L-NMA in J774A.1 C.1 cells could also partially restore intracellular growth inhibition of M. microti caused by IFN-gamma and LPS. TNF-alpha is probably required for the production of NO in J774A.1 cells by IFN-gamma and LPS but TNF-alpha and NO are independently involved in the killing of intracellular M. microti with IFN-gamma and LPS.

Animals↗

Hypoglycemia in small for gestational age babies.

The main objectives of the study were to find the incidence and risk factors associated with development of hypoglycemia in small for gestational age (SGA) babies, to compare haemoglucotest strips (Boehringer Mannheim) with the standard laboratory method (glucose-hexokinase) for estimation of blood glucose, and to measure the insulin and cortisol responses of SGA babies. This was a prospective longitudinal study. The sample included SGA babies and over a period of six months, 127 consecutively born small for gestational age babies were investigated prospectively for development of hypoglycemia in first 48 hrs of life. Plasma samples were taken during episodes of hypoglycemia for insulin and cortisol estimation and compared with non-hypoglycemic controls. The overall incidence of hypoglycemia was 25.2% in SGA babies and 98% of the episodes occurred within first 24 hrs. Compared to non-hypoglycemics, mothers of hypoglycemic babies had higher incidence of receiving i.v. fluids (5% dextrose) during labour. The hypoglycemic babies were more likely to be sick and oral feeds had been initiated by one hour of life in only 37% of them compared to 63% of non-hypoglycemic babies. Plasma insulin/glucose ratio was significantly higher in hypoglycemic than non-hypoglycemic babies, whereas the cortisol levels were similar. Small for gestational age babies are highly prone to develop hypoglycemia in first 24 hrs of life.

Blood Glucose↗

Studies on nutritional and oxygen requirements for production of L-asparaginase by Enterobacter aerogenes.

The carbon and nitrogen sources most suitable for L-asparaginase production by Enterobacter aerogenes were selected and their concentrations optimized in shake-flask cultures. Sodium citrate (1.0%) and diammonium hydrogen phosphate (0.16%) proved to be the best sources of carbon and nitrogen, respectively. Nitrogen catabolite repression of enzyme formation was absent in this bacterium. Cultivation in a reactor showed that the dissolved oxygen level is the limiting factor for L-asparaginase production by E. aerogenes. Glucose was found to be a repressor of enzyme synthesis. Asparagine was absent intracellularly when the L-asparaginase level was high. An increase in the extracellular alanine level when the dissolved oxygen remained low indicated a shift from aerobic to fermentative metabolism.

Aerobiosis↗

Studies on codon usage in Entamoeba histolytica.

Codon usage bias of Entamoeba histolytica, a protozoan parasite, was investigated using the available DNA sequence data. Entamoeba histolytica having AT rich genome, is expected to have A and/or T at the third position of codons. Overall codon usage data analysis indicates that A and/or T ending codons are strongly biased in the coding region of this organism. However, multivariate statistical analysis suggests that there is a single major trend in codon usage variation among the genes. The genes which are supposed to be highly expressed are clustered at one end, while the majority of the putatively lowly expressed genes are clustered at the other end. The codon usage pattern is distinctly different in these two sets of genes. C ending codons are significantly higher in the putatively highly expressed genes suggesting that C ending codons are translationally optimal in this organism. In the putatively lowly expressed genes A and/or T ending codons are predominant, which suggests that compositional constraints are playing the major role in shaping codon usage variation among the lowly expressed genes. These results suggest that both mutational bias and translational selection are operational in the codon usage variation in this organism.

Animals↗

Bone-muscle strength indices for the human lower leg.

This cross-sectional study is based on images from the lower leg as assessed by peripheral quantitative computer tomography (pQCT). Measurements were performed in 39 female and 38 male control subjects and 15 female professional volleyball players, all between 18 and 30 years of age. The images were obtained at shank levels of 4%, 14%, 33%, and 66% from the distal end. Bone and muscle cross-sectional areas, and the bones' density-weighted area moment of resistance and of inertia were assessed. From these, muscle-bone strength indices (MBSIs) were developed for compression (CI = 100. bone area/muscle area) and bending (BI = 100. bone area moment of resistance/muscle area/tibia length). Significant correlations between muscle cross-sectional area and bone were found at all section levels investigated. The strongest correlation for compression was observed in the sections at 14% (correlation coefficient r = 0.74), where 4.10 +/- 0.46 cm(2) bone, on average, was related to 100 cm(2) muscle. The compression index (CI) at the 14% level was independent of the tibia length. Interestingly, the 15 athletes had significantly greater CIs than the control subjects. This is most probably due to the greater tension development in the athletes. The highest correlation for bending was for anteroposterior bending at 33% of tibia length (r = 0.81), where the area moment of resistance, R, was on, average, 4.21 +/- 0.54 cm(3)/100 cm(2) muscle/m tibia length. Analysis of the bones' area moment of inertia showed that buckling is a possible cause of bending at the 33% and 66% levels, but not at the 14% level. No gender differences in MBSI were found. Likewise, age was without significant effect. The data show that bone architecture depends critically on muscle cross section and tension development. Moreover, bone geometry (e.g., the tibia length) influences the geometrical distribution of bone mineral, as it was found that long bones adapted to the same compressive strength are wider than short ones. We conclude that MBSIs offer a powerful diagnostic tool for bone disorders and may contribute to improving the treatment of bone metabolic and other diseases.

Absorptiometry, Photon↗

Gastropathy and defense mechanisms in common bile duct ligated portal hypertensive rats.

Portal hypertensive gastropathy is associated with a broad spectrum of gastric mucosal damage inspite of decreased gastric acid secretion, suggestive of compromised endogenous protective mechanisms. To determine the mechanisms of damage in portal hypertensive gastropathy we measured lipid peroxidation, glutathione, antioxidant and lysosomal enzymes in gastric mucosal homogenates from male Wistar rats with elevated intrasplenic pulp pressure, eighteen days after common bile duct ligation. Thiobarbituric acid-reactive substances and lysosomal enzymes (beta-glucuronidase and acid phosphatase) were increased in the common bile duct ligated group as compared to the sham-operated group. The levels of antioxidant defense enzymes, superoxide dismutase, glutathione peroxidase, catalase and glutathione were decreased as compared to the sham-operated controls. Pre-operative vitamin E administration decreased mucosal lipid peroxidation increased the levels of antioxidant defense enzymes and lowered the lysosomal enzymes. The plasma vitamin E levels in this group were lower when compared to animals receiving it post-operatively. In conclusion, free radical and lysosomal enzyme mediated damage may play a role in portal hypertensive gastropathy.

Animals↗

Signal transduction mechanism in human neutrophil: comparative study between the zeta and beta-protein kinase isotypes.

Role of protein kinase C (PKC) isotypes in the regulation of neutrophil function are not clearly known. In the present study we purified the beta-PKC and zeta-PKC isotypes from human neutrophil. Both the isotypes are immunoreactive only to their respective antibodies. Zeta-PKC was further confirmed by RT-PCR using specific primer. Co-factor requirements for both the kinases were found to be different when DG and ceramide were used as second messenger. Selective substrate specificities were determined for both beta and zeta-PKC using isotype specific pseudosubstrates viz., [Ser25]PKC[19-31] and [Ser119]PKC[113-130] respectively. Endogenous protein phosphorylation by purified beta-PKC and zeta-PKC showed their functional differences in neutrophil. Beta-PKC phosphorylated 13, 15, 19, 33, 36, 47, 80 and 92 kDa proteins and zeta-PKC phosphorylated 19, 22, 42, 47, 75 and 87 kDa proteins, only exception was the phosphorylation of 47 kDa protein which had been phosphorylated by both the kinases. Differences in phosphorylation between beta-PKC and zeta-PKC clearly indicate the selective role for these PKC isotypes in the activation sequences of neutrophil.

Base Sequence↗

Effect of supplementation of vitamin E, selenium and their different combinations on the performance and immune response of broilers.

1. The effect of dietary vitamin E, selenium (Se) and their different combinations on body weight gain, food consumption, food conversion efficiency, leukocyte migration inhibition and antibody production was determined in broilers. 2. Chicks were fed on maize-soya bean based diets with concentrations of supplemental vitamin E varying from 0 to 300 IU/kg and selenium concentrations varying from 0 to 1 mg/kg either alone or in combination from 1 to 42 d of age. 3. The chicks were immunised for Newcastle Disease Virus (NDV) vaccine at 21 d. Per cent leukocyte migration inhibition (LMI) was studied on 42 d. Antibodies to NDV in serum were determined at 10 and 21 d post immunisation (PI). 4. Chicks receiving Se, 1 mg/kg and vitamin E 300 IU/kg had significantly higher cellular immune responses in terms of per cent LMI. 5. Maximum body weight gain and best efficiency of food utilisation were obtained in chicks fed diets containing 0.50 mg/kg Se and 300 IU/kg vitamin E. 6. Significantly higher antibody titres (HI and ELISA) at 10 d PI were attributed to 0.06 mg/kg and 150 IU/kg Se and vitamin E, respectively. 7. These data suggest that optimum growth and immune response may be achieved at supplemental level of Se of 0.06 mg/kg and vitamin E at 150 IU/kg. The vitamin E level is higher than that recommended by NRC (1984, 1994).

Animals↗

Membrane surface of Mycobacterium microti-infected macrophages antigenically differs from that of uninfected macrophages.

Identification of the antigenic changes in mycobacteria-infected macrophage may be important in understanding the mechanisms responsible for the intracellular survival of the bacteria. In the present study, Mycobacterium microti-infected macrophages were utilized to investigate the possibility of differentiating the infected cells from normal cells, based on the antigenic changes occurring in the membranes. Antisera were generated against bacterial extract, heat-killed bacteria and crude preparation of M. microti-infected homologous macrophage membrane. The reactivity of these antisera, towards in vitro infected macrophages, was compared by flow cytometry. Unlike anti-bacterial extract antiserum or anti-heat-killed bacterial antiserum, anti-infected macrophage membrane antiserum reacted with infected macrophage surface. This reactivity increased with the increase in post-infection time. However, it was not observed with uninfected macrophages, PMA- or lipopolysaccharide-activated macrophages and those harboring Mycobacterium tuberculosis H37Ra, heat-killed M. microti and Leishmania donovani. Interestingly, anti-infected macrophage membrane antiserum identified a 63-kDa antigen in M. microti-infected macrophage membranes which was not present in the membranes of normal macrophages, activated macrophages and of those infected with M. tuberculosis H37Ra, heat-killed M. microti and L. donovani. Thus, membranes of M. microti-infected macrophages differ antigenically from those of the normal macrophages and infected homologous macrophage membrane antiserum provides a useful tool in studying such changes.

Animals↗

In vivo assessment of trabecular bone structure using fractal analysis of distal radius radiographs.

Our purpose in this study was (i) to measure trabecular bone structure using fractal analysis of distal radius radiographs in subjects with and without osteoporotic hip fractures, and (ii) to compare these measures with bone mineral density (BMD) as well as with measures of trabecular bone structure derived from high resolution magnetic resonance (MR) images. Distal radius radiographs were obtained using semi-industrial films (55 kVp, 400 mAs) in 30 postmenopausal patients, who had suffered osteoporotic hip fractures (74.8+/-8.2 years) in the last 24 months and 27 postmenopausal age-matched (74.6+/-6.6 yr) normal volunteers. Radiographs were digitized at 50 microm. A Fourier power spectrum-based fractal dimension (FD) characterizing the trabecular pattern was measured in a region of interest proximal to the joint line. The fractal dimension was calculated over two spatial frequency (f) ranges: FD1 was calculated over 0.5<log(f)<l.0, FD2 over the higher range 1.0<log(f)<1.5. Trabecular BMD in the radius was obtained using peripheral quantitative computed tomography (pQCT) (Stratec GmbH, Germany). In addition BMD of the proximal femur was determined using dual x-ray absorptiometry (DXA) (QDR 2000, Hologic, MA). In a subset of patients (16 controls and 18 with hip fractures), high resolution MR imaging of the distal radius (spatial resolution of 156 x 156 x 500 microm) was used to obtain measures analogous to bone histomorphometry. There were significant differences (p<0.05) between the fracture and nonfracture groups in the total femur BMD (13%), trabecular BMD in the distal radius (4%), and the fractal dimension in the radiographs (FD2) (3%). The correlations between FD2 and the total femur BMD as well as trabecular bone BMD in the distal radius were -0.48 (p<0.006) and -0.22 (p<0.33); respectively; FD1 increased with BMD and showed lower correlations. FD2 showed good correlations with App. Tb.N (-0.71) and App. Tb.Sp (0.69) (p<0.01), moderate correlation with App BV/TV (-0.53) (p<0.05), and no significant correlation with App. Tb.Th. The correlations between structural measures and FD1 showed the inverse trend and were typically lower. The odds ratios for a hip fracture were 2.44 for total femur BMD, 1.5 for trabecular BMD (radius), and 1.5 for FD2, respectively. In summary, the fractal measures derived from radiographs of the radius show differences between subjects with and without hip fractures, the predictive power of measures in the distal radius are comparable to radial trabecular BMD but lower than that of total hip BMD.

Aged↗

Use of an attenuated leishmanial parasite as an immunoprophylactic and immunotherapeutic agent against murine visceral leishmaniasis.

The ability of the leishmanial parasite UR6 to act as an immunoprophylactic and immunotherapeutic agent against Leishmania donovani infection in BALB/c mice was investigated. Unlike the virulent L. donovani AG83 (MOHOM/IN/1983/AG83), UR6 given through intracardiac route failed to induce visceral infection, but when it was injected subcutaneously, UR6 induced a short-lived and localized self-healing skin lesion. Priming of peritoneal macrophages with UR6 in vitro induced superoxide (O(2)(-)) generation, whereas similar experiments with virulent AG83 inhibited O(2)(-) generation. It was observed that priming of mice with either live or sonicated UR6 in the absence of any adjuvant provided strong protection against subsequent virulent challenge. Further, UR6-primed infected mice not only displayed a strong antileishmanial delayed-type hypersensitivity (DTH) response but also showed an elevated level of the serum antileishmanial immunoglobulin G2a (IgG2a) isotype, whereas infected mice failed to mount any antileishmanial DTH response and showed an elevated level of IgG1. This indicates that UR6 priming and subsequent L. donovani infection allowed the expansion of Th1 cells. Our studies indicate that UR6 has potential to be used as an immunoprophylactic and immunotherapeutic agent against experimental visceral leishmaniasis.

Animals↗

Use of RNA arbitrarily primed-PCR fingerprinting to identify Vibrio cholerae genes differentially expressed in the host following infection.

Evidence suggests that a repertoire of Vibrio cholerae genes are differentially expressed in vivo, and regulation of virulence factors in vivo may follow a different pathway. Our work was aimed at characterization of in vivo-grown bacteria and identification of genes that are differentially expressed following infection by RNA arbitrarily primed (RAP)-PCR fingerprinting. The ligated rabbit ileal loop model was used. The motility of in vivo-grown bacteria increased by 350% over that of in vitro-grown bacteria. Also, the in vivo-grown cells were more resistant to killing by human serum. By using the RAP-PCR strategy, five differentially expressed transcripts were identified. Two in vitro-induced transcripts encoded polypeptides for the leucine tRNA synthatase and the 50S ribosomal protein, and the three in vivo-induced transcripts encoded the SucA and MurE proteins and a polypeptide of unknown function. MurE is a protein involved in the peptidoglycan biosynthetic pathway. The lytic profiles of in vivo- and in vitro-grown cells suspended in distilled water were compared; the former was found to be slightly less sensitive to lysis. Ultrathin sections of both cells observed under the transmission electron microscope revealed that in contrast to the usual wavy discontinuous membrane structure of the in vitro-grown cells, in vivo-grown cells had a more rigid, clearly visible double-layered structure. The V. cholerae murE gene was cloned and sequenced. The sequence contained an open reading frame of 1,488 nucleotides with its own ribosome-binding site. A plasmid containing the murE gene of V. cholerae was transformed into V. cholerae 569B, and a transformed strain, 569BME, containing the plasmid was obtained. Ultrathin sections of 569BME viewed under a transmission electron microscope revealed a slightly more rigid cell wall than that of wild-type 569B. When V. cholerae 569B and 569BME cells were injected separately into ligated rabbit ileal loops, the transformed cells had a preference for growth in the ileal loops versus laboratory conditions.

Amino Acid Sequence↗

RegA, iron, and growth phase regulate expression of the Pseudomonas aeruginosa tol-oprL gene cluster.

The tol-oprL region in Pseudomonas aeruginosa appears to be involved in pyocin uptake and required for cell viability. The complete nucleotide sequences of the tolQRA and oprL genes as well as the incomplete sequences of tolB and orf2 have been previously reported. In addition, the sequence of a P. aeruginosa iron-regulated gene (pig6) has been described and found to share homology with an open reading frame located upstream of the Escherichia coli tolQRA genes (U. A. Ochsner and M. L. Vasil, Proc. Natl. Acad. Sci. USA 93:4409-4414, 1996). In this study, we cloned the remainder of the P. aeruginosa tol-oprL gene cluster and determined its nucleotide sequence. This cluster was found to consist of seven genes in the order orf1 tolQ tolR tolA tolB oprL orf2. Transcriptional analysis of this gene cluster was performed by detecting the presence of mRNAs spanning adjacent genes as well as by using a promoterless lacZ reporter gene fused to each of the seven genes contained in the tol-oprL locus. The results show that there are three major transcriptional units or operons in this region, orf1-tolQRA, tolB, and oprL-orf2, in contrast to the E. coli tol-pal region, where there are only two operons, orf1-tolQRA and tolB-pal-orf2. Analysis of gene expression indicated that the tol-oprL genes of P. aeruginosa are both iron and growth phase modulated. The first operon, orf1-tolQRA, is iron regulated throughout growth, but iron-regulated expression of tolB and oprL fusions occurs only in late log phase. The expression of the three operons was significantly less repressed by iron in fur mutants than in the wild-type strain, suggesting the involvement of Fur in the iron regulation of all three operons. RegA is a positive yet nonessential regulator of tol-oprL expression.

Bacterial Outer Membrane Proteins↗

Changes in calcaneal trabecular bone structure after heart transplantation: an MR imaging study.

PURPOSE: To use high-spatial-resolution magnetic resonance (MR) imaging to analyze the trabecular bone structure of the calcaneus in patients before and after heart transplantation and to compare this technique with bone mineral density (BMD) measurement in predicting therapy-induced bone loss and vertebral fracture status. MATERIALS AND METHODS: High-spatial-resolution 1.5-T MR imaging of the calcaneus was performed in 40 men 11-120 months after heart transplantation, in 11 men before heart transplantation, and in 10 age-matched male volunteers. Sagittal and transverse T1-weighted spin-echo images with a voxel size of 0.195 x 0.195 x 1.000 mm were obtained, and structure measurements analogous to bone histomorphometric values were calculated. In addition, the BMD of the lumbar spine was determined in the transplant recipients pre- and postoperatively by using quantitative computed tomography, and vertebral fracture status was assessed. RESULTS: Significant differences in structure and BMD measurements were found between patients before and after heart transplantation (P <. 05). In 17 (42%) of 40 transplant recipients, vertebral fractures were found. Although structure measurements were significantly different between patients with and those without fractures (P <.05), BMDs were not. Correlations between time after transplantation and some structure measurements were moderately significant (P <. 05), but such correlations with BMD measurements were not. CONCLUSION: MR imaging-derived structure measurements in the calcaneus are useful for monitoring bone changes after heart transplantation and assessing vertebral fracture status.

Adult↗

Advanced imaging of the macrostructure and microstructure of bone.

Noninvasive and/or nondestructive techniques are capable of providing more macro- or microstructural information about bone than standard bone densitometry. Although the latter provides important information about osteoporotic fracture risk, numerous studies indicate that bone strength is only partially explained by bone mineral density. Quantitative assessment of macro- and microstructural features may improve our ability to estimate bone strength. The methods available for quantitatively assessing macrostructure include (besides conventional radiographs) quantitative computed tomography (QCT) and volumetric quantitative computed tomography (vQCT). Methods for assessing microstructure of trabecular bone noninvasively and/or nondestructively include high-resolution computed tomography (hrCT), micro-computed tomography (muCT), high-resolution magnetic resonance (hrMR), and micromagnetic resonance (muMR). vQCT, hrCT and hrMR are generally applicable in vivo; muCT and muMR are principally applicable in vitro. Although considerable progress has been made in the noninvasive and/or nondestructive imaging of the macro- and microstructure of bone, considerable challenges and dilemmas remain. From a technical perspective, the balance between spatial resolution versus sampling size, or between signal-to-noise versus radiation dose or acquisition time, needs further consideration, as do the trade-offs between the complexity and expense of equipment and the availability and accessibility of the methods. The relative merits of in vitro imaging and its ultrahigh resolution but invasiveness versus those of in vivo imaging and its modest resolution but noninvasiveness also deserve careful attention. From a clinical perspective, the challenges for bone imaging include balancing the relative advantages of simple bone densitometry against the more complex architectural features of bone or, similarly, the deeper research requirements against the broader clinical needs. The considerable potential biological differences between the peripheral appendicular skeleton and the central axial skeleton have to be addressed further. Finally, the relative merits of these sophisticated imaging techniques have to be weighed with respect to their applications as diagnostic procedures requiring high accuracy or reliability on one hand and their monitoring applications requiring high precision or reproducibility on the other.

Animals↗